First Online: 28 November 2001Received: 24 September 2001Accepted: 28 November 2001

Abstract

BackgroundRecently a hyperthermic rat hippocampal slice model system has been used to investigate febrile seizure pathophysiology. Our previous data indicates that heating immature rat hippocampal slices from 34 to 41°C in an interface chamber induced epileptiform-like population spikes accompanied by a spreading depression SD. This may serve as an in vitro model of febrile seizures.

ResultsIn this study, we further investigate cellular mechanisms of hyperthermia-induced initial population spike activity. We hypothesized that GABAA receptor-mediated 30–100 Hz γ oscillations underlie some aspects of the hyperthermic population spike activity. In 24 rat hippocampal slices, the hyperthermic population spike activity occurred at an average frequency of 45.9 ± 14.9 Hz Mean ± SE, range = 21–79 Hz, n = 24, which does not differ significantly from the frequency of post-tetanic γ oscillations 47.1 ± 14.9 Hz, n = 34 in the same system. High intensity tetanic stimulation induces hippocampal neuronal discharges followed by a slow SD that has the magnitude and time course of the SD, which resembles hyperthermic responses. Both post-tetanic γ oscillations and hyperthermic population spike activity can be blocked completely by a specific GABAA receptor blocker, bicuculline 5–20 μM. Bath-apply kynurenic acid 7 mM blocks synaptic transmission, but fails to prevent hyperthermic population spikes, while intracellular diffusion of QX-314 30 mM abolishes spikes and produces a smooth depolarization in intracellular recording.